1. Field of the Invention
The present invention relates generally to sample cartridge blocks and more specifically to such blocks which are capable of providing improved sample temperature characteristics and increased sample density.
2. Discussion of the Related Art
A variety of biochemical experiments, involve monitoring certain temperature sensitive reactions. Typically, such studies include thermal cycling of the sample. Such experiments include: nucleic acid hybridizations, polymerase chain reaction (PCR) and its variants (e.g., RT-PCR), isothermal amplification techniques (e.g., "NASBA", "In-Situ-3SR", "PRINS"), cycling "PRINS" and antigen based detection of tissue features. These procedures and general background are contained in the following literature references: Current Protocols in Molecular Biology, F. M. Ausubel, et al., eds., John Wiley & Sons, Inc. Sections 14.3 and 14.7; Current Protocols in Molecular Biology, F. M. Ausubel, et al., eds., John Wiley & Sons, Inc., Section 14.8; Steacker, H., M. Cammer, R. Rubenstein and T. R. Van de Water. 1994. A procedure for RT-PCR Amplification of mRNAs on Histological Specimens. BioTechniques. 16:76-80; Sooknanan, R. And L. T. Malek. 1995. NASBA. A detection and amplification system uniquely suited for RNA. Bio/Technology. 13:563-564; Zehba, I., G. W. Hacker, J. F. Sallstrom, E. Rylander and E. Wilander. 1992. Self sustained sequence replication-based amplification (3SF) for the in situ detection of MRNA in cultured cells. Cell Vision. 1:20-24; Gosden, J., D. Hanratty, J. Starling, J. Fantes, A. Mitchell, and D. Porteous. 1991. Oligonucleotide-primed in situ DNA synthesis (PRINS): a method for chromosome mapping, banding and investigation of sequence organization. Cytogenet. Cell Genet. 57:100-104; Watkins, S. Immunohistochemistry. in: Current Protocols in Molecular Biology, F. M. Ausubel, et al., eds., John Wiley & Sons, Inc., Section 14.6. In such studies, the sample may be rapidly or slowly cycled among a variety of temperatures ranging up to nearly 100.degree. C.
Accordingly, various sample cartridges, such as microscope slides, are used in large volumes in both industry and academia. As a result, studying individual sample cartridges can be both tedious and inefficient. Therefore, sample blocks, devices that are capable of holding several sample cartridges, are often used. To optimize efficiency and economy, it is typically desirable to utilize sample cartridge blocks that are capable of holding or containing a relatively large number of samples and/or sample cartridges.
In a variety of circumstances, it is desirable to use a sample cartridge block that can monitor and control the temperature of a sample cartridge contained within the sample cartridge block. Therefore, sample blocks are typically capable of providing temperature control of the sample cartridges. When using a temperature controller in conjunction with a sample cartridge block, it is often advantageous to minimize temperature gradients throughout the three dimensional volume defined by the sample cartridge block so that the temperature of each sample cartridge contained within the sample cartridge block can be controlled to within some acceptable range of temperatures.
Typically, it is advantageous for a sample cartridge block to be capable of changing the temperature of a sample or sample cartridge at a relatively high rate while maintaining a relatively low thermal gradient throughout the sample cartridge block. To achieve this goal, a sample block should preferably include a material that has a relatively high thermal conductance. In order to achieve this goal, it is desirable for the surface area of the sample cartridge block in contact with the temperature controller to be comparatively high.
One known prior art sample cartridge block, designed for the Perkin Elmer Gene Amp In Situ 100 System, includes a horizontal base plate and sample plates which project vertically from the base plate to form a comb-like structure. A spring is located within each slot to hold the sample cartridges in place within the sample block. However, since the sample cartridges are placed vertically within the sample block, special sample cartridges must be used which reduce or eliminate the possibility of sample leakage due to gravity. Moreover, this sample block design allows the temperature of the slides to be controlled from only one side. As a result, asymmetric heating of the samples occurs due to a thermal gradient, and the temperature stability of the samples and/or sample cartridges is limited. Furthermore, this design offers a relatively poor heat pump area to thermal mass ratio, resulting in inefficient heating. Thus, the sample block has a relatively complex design and provides relatively poor sample temperature control characteristics.
Another sample cartridge block, designed for the Hybaid OmniSlide thermal cycler, includes an essentially planar surface and recessions. The recessions are designed to hold sample cartridges in a side-by-side fashion. This arrangement results in a relatively small cartridge density. In addition, precise temperature control of samples and sample cartridges is difficult because the cartridges must be separated by a distance of at least the width of a sample cartridge. Furthermore, the temperature of the sample block is controlled from the undersurface only, and heating occurs by electrical resistance and cooling is achieved by forced air flow. As a result, the sample cartridge block provides comparatively poor sample temperature characteristics. Moreover, with this design, good thermal control of the sample cartridges would require a separate sensor and independent temperature control for each sample cartridge. Hence, this sample block provides a relatively low sample density and comparatively poor sample temperature control characteristics.
An additional design for a sample block, the MJ Research PTC-100-16MS, includes a stacked, two-dimensional array of sample cartridge slots machined into a sample block. In addition, a temperature control device is located at the underside of the sample block only, so heat flow across the sample block is asymmetric. Thus, there is usually a temperature gradient across the sample cartridge block. To reduce the temperature gradient across the sample block, a relatively low rate of heating and cooling must be used, but this can reduce the utility of the sample cartridge block. Accordingly, this arrangement provides limited sample temperature control.
Thus, it remains a desirable in the art to provide a sample block having a design that affords high sample cartridge density while avoiding uneven heating of samples and/or sample cartridges due to thermal gradients. It is a further challenge in the art to provide a sample block that allows sample cartridges to be stacked horizontally. Furthermore, it is a general problem to design a sample cartridge block that has good mechanical integrity yet also has a relatively low thermal mass. Typically, low thermal mass materials provide comparatively poor mechanical integrity. Hence, it would be advantageous to provide a sample cartridge block designed to reduce or eliminate the significance of having good mechanical integrity.